1. 1 Genome Rearrangements João Meidanis São Paulo, Brazil December, 2004

2. 2 AGENDA 1.Summary 2.Genome comparison 3.Rearrangement events 4.Example: mouse vs. human (X-chromosome) 5.Rearrangement distance 6.Known results 7.Current research lines

3. 3 One of the big challenges of contemporary Biology is to measure evolution Besides point mutations, evolution is known to occur by means of movements of large chunks of DNA (genome rearrangements) The advent of entire genomes brings a whole new facet to this issue As a first estimate of the amount of evolution between two species, one can use the formula number of events unit of time Our research focus on efficient ways of computing the number of rearrangement events between two or more genomes SUMMARY

4. 4 AGENDA 1.Summary 2.Genome comparison 3.Rearrangement events 4.Example: mouse vs. human (X-chromosome) 5.Rearrangement distance 6.Known results 7.Current research lines

5. 5 GENOME COMPARISON Point mutations...TATCGATAGACCACTG......TATC--TAGACGACTA...

6. 6 GENOME COMPARISON Genome rearragements A B C D E F G H A B C D E F G H Movement of large segments within the genome. Above, segment E – F – G flips over

7. 7 AGENDA 1.Summary 2.Genome comparison 3.Rearrangement events 4.Example: mouse vs. human (X-chromosome) 5.Rearrangement distance 6.Known results 7.Current research lines

8. 8 REARRANGEMENT EVENTS Insertion / Deletion Reversal Transposition Fission / Fusion Block Interchange Others: duplication, genome doubling

9. 9 INSERTION / DELETION Gene gain / loss between genomes AB C D E FG H I J AB C D E G H I J

10. 10 REVERSAL A segment is reversed between genomes AB C D E FG H I J AB C D E F G H I J

11. 11 TRANSPOSITION A segment moves to a new position (or: exchange of two adjacent segments) AB C D E FG H I J AB E F G CD H I J

12. 12 FISSION / FUSION Genome breaks in two / Two genomes join AB C D E FG H I J A B C D E F G H I J

13. 13 BLOCK INTERCHANGE Exchange of two nonadjacent segments AB C D E FG H I J AB G H E FC D I J

14. 14 AGENDA 1.Summary 2.Genome comparison 3.Rearrangement events 4.Example: mouse vs. human (X-chromosome) 5.Rearrangement distance 6.Known results 7.Current research lines

15. 15 Figure 2. X-chromosome: from local similarities, to synteny blocks, to breakpoint graph, to rearrangement scenario EXAMPLE: HUMAN AND MOUSE X-CHROMOSOME Pavel Pevzner et al. Genome Res. 2003; 13: 37-45 Thanks to:

16. 16 AGENDA 1.Summary 2.Genome comparison 3.Rearrangement events 4.Example: mouse vs. human (X-chromosome) 5.Rearrangement distance 6.Known results 7.Current research lines

17. 17 REARRANGEMENT DISTANCE Maximum parsimony approach Given two genomes, and a set of events, the rearrangement distance between the genomes is the length of the shortest series of events that transforms one genome into the other. In the previous example: Genome 1: mouse X-chromosome Genome 2: human X-chromosome Set of events: reversals only Distance: 7 events

18. 18 AGENDA 1.Summary 2.Genome comparison 3.Rearrangement events 4.Example: mouse vs. human (X-chromosome) 5.Rearrangement distance 6.Known results 7.Current research lines

19. 19 KNOWN RESULTS Insertion / Deletion distance: efficient algorithm known Reversal distance : efficient algorithm known Transposition distance: no efficient algorithm known; approximative algorithms Fission / Fusion distance : efficient algorithm known Block Interchange distance : efficient algorithm known

20. 20 AGENDA 1.Summary 2.Genome comparison 3.Rearrangement events 4.Example: mouse vs. human (X-chromosome) 5.Rearrangement distance 6.Known results 7.Current research lines

21. 21 CURRENT RESEARCH LINES Solve transposition distance problem Comparions of three or more genomes Sets with more than one operation, e.g., reversal and transposition distance